Temporal trends in the starting of insulin therapy in type 2 diabetes in Italy: data from the AMD Annals initiative.

AIMS: Opportunities and needs for starting insulin therapy in Type 2 diabetes (T2D) have changed overtime. We evaluated clinical characteristics of T2D subjects undergoing the first insulin prescription during a 15-year-observation period in the large cohort of the AMD Annals Initiative in Italy. METHODS: Data on clinical and laboratory variables, complications and concomitant therapies and the effects on glucose control after 12 months were evaluated in T2D patients starting basal insulin as add-on to oral/non-insulin injectable agents, and in those starting fast-acting in add-on to basal insulin therapy in three 5-year periods (2005-2019). RESULTS: We evaluated data from 171.688 T2D subjects who intensified therapy with basal insulin and 137.225 T2D patients who started fast-acting insulin. Overall, intensification with insulin occurred progressively earlier over time in subjects with shorter disease duration. Moreover, the percentage of subjects with HbA1c levels > 8% at the time of basal insulin initiation progressively decreased. The same trend was observed for fast-acting formulations. Clinical characteristics of subjects starting insulin did not change in the three study-periods, although all major risk factors improved overtime. After 12 months from the starting of basal or fast-acting insulin therapy, mean HbA1c levels decreased in all the three investigated time-periods, although mean HbA1c levels remained above the recommended target. CONCLUSIONS: In this large cohort of T2D subjects, a progressively earlier start of insulin treatment was observed during a long observation period, suggesting a more proactive prescriptive approach. However, after 12 months from insulin prescription, in many patients, HbA1c levels were still out-of-target.

The Italian Society of Andrology and Sexual Medicine (SIAMS), along with ten other Italian Scientific Societies, guidelines on the diagnosis and management of erectile dysfunction.

PURPOSE: Erectile dysfunction (ED) is one of the most prevalent male sexual dysfunctions. ED has been in the past mistakenly considered a purely psycho-sexological symptom by patients and doctors. However, an ever-growing body of evidence supporting the role of several organic factors in the pathophysiological mechanisms underlying ED has been recognized. METHODS: The Italian Society of Andrology and Sexual Medicine (SIAMS) commissioned an expert task force involving several other National Societies to provide an updated guideline on the diagnosis and management of ED. Derived recommendations were based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. RESULTS: Several evidence-based statements were released providing the necessary up-to-date guidance in the context of ED with organic and psychosexual comorbidities. Many of them were related to incorrect lifestyle habits suggesting how to associate pharmacotherapies and counseling, in a couple-centered approach. Having the oral therapy with phosphodiesterase type 5 inhibitors as the gold standard along with several other medical and surgical therapies, new therapeutic or controversial options were also discussed. CONCLUSIONS: These are the first guidelines based on a multidisciplinary approach that involves the most important Societies related to the field of sexual medicine. This fruitful discussion allowed for a general agreement on several recommendations and suggestions to be reached, which can support all stakeholders in improving couple sexual satisfaction and overall general health.

Italian Titration Approach Study (ITAS) with insulin glargine 300 U/mL in insulin-naïve type 2 diabetes: Design and population.

BACKGROUND AND AIMS: Fostering patient's self-managing of basal insulin therapy could improve glucose control, by removing patient's and physician's barriers to basal insulin initiation, titration and glucose monitoring. The Italian Titration Approaches Study (ITAS) aims at demonstrating non-inferiority (<0.3% margin) in efficacy of glucose control (change in glycated hemoglobin [HbA1c] after 24 weeks) by the same titration algorithm of insulin glargine 300 U/mL (Gla-300), managed by the (nurse assisted) patient versus the physician, in insulin naïve patients with Type 2 Diabetes Mellitus (T2DM), uncontrolled with previous treatments. METHODS AND RESULTS: ITAS is a phase IV, 24-week, national, multicenter, open label, randomized (1:1) parallel group study. 458 patients were enrolled, 359 randomized, and 339 completed the study, in 46 Italian centers. Baseline characteristics and previous medications of the ITT population (N = 355) are reported. Mean ± SD age, T2DM duration, HbA1c, FPG and BMI were 64.0 ± 9.8 years, 11.6 ± 7.6 years, 8.79 ± 0.65%, 170.9 ± 42.3 mg/dL, and 30.3 ± 5.6 kg/m2, respectively. Vascular and metabolic disorders were most frequent (73.8% and 58.3%, respectively). More than 90% of patients were on metformin. CONCLUSION: ITAS is the first study to compare two different managers (nurse-assisted patient vs physician) of the same titration algorithm of Gla-300 in insulin naïve patients with T2DM in unsatisfactory glucose control. This study might provide novel evidence on the efficacy/effectiveness of patient-managed titration algorithm of Gla-300 in a pragmatic setting and may reduce barriers to basal insulin initiation and its titration.

Diabetic neuropathy is not associated with homocysteine, folate, vitamin B12 levels, and MTHFR C677T mutation in type 2 diabetic outpatients taking metformin.

BACKGROUND: Hyperhomocysteinemia and vitamin B12 deficiency may be involved in the development of diabetic peripheral neuropathy (DPN). Metformin therapy may reduce vitamin B12 plasma levels, thus contributing to DPN. AIM AND METHODS: The purposes of this cross-sectional study were to assess (1) the potential associations of DPN with serum levels of homocysteine (tHcy), B-vitamins, and/or the common methylenetetrahydrofolate reductase (MTHFR) C677T mutation; (2) the influence of chronic treatment with metformin on tHcy and B-vitamins concentrations and, finally, (3) to evaluate whether, by this influence, metformin is a risk factor for DPN in a group of type 2 diabetic outpatients. RESULTS: Our data showed that fasting tHcy, folate, and vitamin B12 levels and the MTHFR C677T genotype distribution were comparable between subjects with (n = 79, 30 %) and without DPN (n = 184, 70 %). Metformin-treated subjects (n = 124, 47 %) showed significantly lower levels of vitamin B12 (P < 0.001), but the prevalence of DPN was not different when compared to those not treated with this drug (33 vs. 27 %, P = NS). At univariate regression analysis, DPN was associated with age, duration of diabetes, HbA1c, creatinine levels, and the presence of coronary heart disease (CHD), and negatively with HDL-C concentrations (P < 0.05 all), but at multivariate regression analysis, high creatinine levels (P = 0.06), low HDL-C levels (P = 0.013), and a higher prevalence of CHD (P = 0.001) were the only variables independently associated with DPN in this population. CONCLUSIONS: In conclusion, in these type 2 diabetic outpatients circulating levels of tHcy, folate, and the MTHFR C677T mutation are not associated with DPN, which was predicted by creatinine levels, CHD, and dyslipidemia. Metformin therapy is associated with a mild vitamin B12 level reduction, but not with DPN.

Incretin-based therapy and acute cholecystitis: a review of case reports and EudraVigilance spontaneous adverse drug reaction reporting database.

WHAT IS KNOWN AND OBJECTIVE: Glucagon-like peptide-1 (GLP-1) receptor agonists delay gastric and bowel emptying. A similar inhibitory effect of GLP-1 on gallbladder motility has been suggested, possibly leading to an increased risk of cholecystitis related to incretin-based medications, which include GLP-1 antagonists. Our objective was to review evidence in EudraVigilance, the European spontaneous reporting database and the scientific literature on this issue. COMMENT: Increasing evidence suggests an association of incretins with gallbladder adverse events. Pharmacovigilance data from EudraVigilance includes 200 serious ADR reports concerning cholecystitis related to the use of incretin-based therapies. Several mechanisms may explain this increased risk of cholecystitis, including rapid weight loss, inhibition of gallbladder contraction and emptying, reduced bile acids production, modulation of inflammation. WHAT IS NEW AND CONCLUSIONS: The available data suggest the possibility of gallbladder disease in diabetic subjects treated with incretins and highlight the importance of evaluating risk factors for cholelithiasis and gallbladder diseases in patients with diabetes before starting this therapy.

Twelve-month treatment with Liraglutide ameliorates Visceral Adiposity Index and common cardiovascular risk factors in type 2 diabetes outpatients.

AIM: In addition to the effects on glycemic control and body weight, GLP-1 receptor agonists may favorably affect other major cardiovascular disease (CVD) risk factors, although currently available data are still sparse. In this retrospective study, we evaluated the effects of 12-month treatment with liraglutide on major CVD risk factors in 115 type 2 diabetes outpatients (60 men and 55 women), on stable hypoglycemic, anti-hypertensive and/or lipid-lowering therapy. METHODS: Clinical and anthropometric data, metabolic and lipid profile, as well as the Visceral Adiposity Index (VAI), an obesity-related CVD risk factor, were measured in all participants at baseline and after 12-month treatment. RESULTS: Treatment with liraglutide was associated with a significant reduction from baseline values of fasting blood glucose (-42.1 mg/dl, P < 0.05), HbA1c (-1.5 %, -17 mmol/mol, P < 0.05), body weight (-7.1 kg, P < 0.05), waist circumference (-6.8 cm, P < 0.001), total-cholesterol (-27.4 mg/dl, P < 0.05), LDL-cholesterol (-25.4 mg/dl, P < 0.05), triglycerides (-56.1 mg/dl, P < 0.05), and non-HDL-C (-36.6 mg/dl, P < 0.05) and an increase of HDL-cholesterol concentrations (+9.3 mg/dl, P < 0.001), a significant reduction in both systolic and diastolic blood pressure (-14.7 mmHg, P < 0.001 and -9.0 mmHg, P < 0.05, respectively) and a decrease of VAI values (-1.6, P < 0.001). All these differences were independent of changes in BMI and comparable in men and women. CONCLUSIONS: In conclusion, 12-month treatment with liraglutide in add-on to on-going hypoglycemic therapy significantly ameliorates all major CVD risk factors and reduces cardiometabolic risk, as estimated by VAI values.

Lipid and non-lipid cardiovascular risk factors in postmenopausal type 2 diabetic women with and without coronary heart disease.

BACKGROUND: Coronary heart disease (CHD) is the leading cause of death in diabetic women. In addition to hyperglycemia, other factors may contribute to the excessive cardiovascular risk. AIM: In this study we evaluated common and emerging risk factors in a selected group of postmenopausal type 2 diabetic women with (n = 36) and without CHD (n = 59), not taking lipid-lowering medications. METHODS: Clinical and lifestyle data were collected, and metabolic and lipid profile, as well as fasting plasma levels of total homocysteine (tHcy), folate, vitamin B12, C-reactive protein (hsCRP), interleukin 6 (IL-6), and vascular cell adhesion molecule-1 (VCAM-1) were measured in all participants. RESULTS: Age, menopause and diabetes duration, family history for cardiovascular disease, prevalence of hypertension and current insulin use were greater in diabetic women with than without CHD (P < 0.05 for all comparisons). CHD women also showed higher levels of triglycerides, small dense LDL (sdLDL), remnant-like particle cholesterol, tHcy, and VCAM-1, and a lower creatinine clearance (P < 0.05 all). Conversely, the two groups were comparable for BMI, waist circumference, smoking habit, fasting plasma glucose, HbA1c, total cholesterol, low-density lipoprotein cholesterol (LDL-C), HDL cholesterol, folate, vitamin B12, hsCRP and IL-6 levels. At multivariate analysis, lower creatinine clearance (OR = 0.932, P = 0.017) and higher sdLDL serum concentration (OR = 1.224, P = 0.037) were the strongest risk factors associated with CHD in this population, whereas no significant association was noted with LDL-C. CONCLUSIONS: Our data suggest that beyond LDL-C, a lower creatinine clearance and more subtle alterations of LDL particles, together with a constellation of several well known and emerging cardiovascular risk factors, are stronger contributors to the high CHD risk of diabetic women.

The SUBITO-DE study: sexual dysfunction in newly diagnosed type 2 diabetes male patients.

INTRODUCTION: No data on the prevalence of erectile dysfunction (ED) in subjects with newly diagnosed Type 2 diabetes mellitus (T2DM) are currently available. AIM: The aim of the present study was to estimate the prevalence of ED and its associated causes in a sample of male patients with recently diagnosed DM (<24 months) attending a diabetes care center. METHODS: The study comprised two phases: a cross-sectional analysis and a longitudinal reassessment of the data collected during the first phase. During the first phase, 1503 subjects (mean age 58.7±8.9 yr) from 27 centers were interviewed: 666 (43.3%) reported experiencing ED, 499 of which (mean age 58.8±8.8 yr) agreed to participate in the study (final enrolment rate, 33.3%). Concurrent morbidities were hypertension (55.3%), dyslipidemia (39.5%), and coronary heart disease (7.8%); chronic complications were neuropathy (8.9%), nephropathy (12.6%) and retinopathy (7.6%) in about one third of the sample at enrolment. RESULTS: Overall, about 20% of the patients reported having used ED drugs, but more than 50% had abandoned therapy because of the drug's ineffectiveness or high cost. The prevalence of hypogonadism was 46.9% (total testosterone level, 3.5 ng/ml). Some 20% of patients reported symptoms suggestive of depression. CONCLUSION: The present study provides data showing a high prevalence of ED, hypogonadism and depressive symptoms among male patients with newly diagnosed T2DM. Further analysis of the data will elucidate the specific determinants of such conditions and their longitudinal significance.

Phalangeal quantitative ultrasound and metabolic control in pre-menopausal women with type 1 diabetes mellitus.

BACKGROUND: Several studies have reported increased fracture risk in Type 1 diabetes mellitus (T1DM). Quantitative Ultrasound (QUS) provides information on the structure and elastic properties of bone, which are important determinants of fracture risk, along with bone mineral density. AIM: To study phalangeal sites by QUS, examine bone turnover markers and analyze association between these factors with metabolic control in a population of pre-menopausal women with T1DM. MATERIAL AND METHODS: Thirty-five T1DM pre-menopausal women (mean age 34.5 ± 6.8 yr) attending the Diabetic Outpatients Clinic in the Department of Internal Medicine, University of Messina, were consecutively enrolled and divided into two groups, taking into account the mean value of glycated hemoglobin in the last three years. Twenty healthy age-matched women served as controls. Phalangeal ultrasound measurements [Amplitude Dependent Speed of Sound (AD-SoS), Ultrasound Bone Profile Index (UBPI), TScore, Z-Score] were performed using a DBM Sonic Bone Profiler. Osteocalcin and deoxypyridinoline served as markers of bone formation and bone resorption, respectively. RESULTS: T1DM women with poor metabolic control showed lower phalangeal QUS values compared to healthy controls (p<0.01) and T1DM women with good metabolic control (p<0.05). No significant differences in QUS measurements were detected between T1DM women with good metabolic control and healthy controls. Lower bone formation and increased bone resorption, although not statistically significant, were observed in patients with poor metabolic control in comparison to patients with good metabolic control. CONCLUSIONS: Poor metabolic control may worsen the quality of bone in T1DM. Phalangeal QUS could be considered as a tool to screen T1DM women for osteoporosis in pre-menopausal age.

Pioglitazone Randomised Italian Study on Metabolic Syndrome (PRISMA): effect of pioglitazone with metformin on HDL-C levels in Type 2 diabetic patients.

BACKGROUND: Previous evidence indicates that pioglitazone may improve dyslipidemia in patients with Type 2 diabetes mellitus (T2DM). AIM: The primary objective of this study was to evaluate the effect of either pioglitazone or placebo with metformin on levels of serum HDL cholesterol (HDL-C) in patients with T2DM. A secondary objective evaluated changes in metabolic syndrome (MS)-specific parameters. SUBJECTS AND METHODS: This multicenter, double-blind, randomized study was performed in patients with T2DM treated with metformin and hemoglobin A1c (HbA1c) levels between 6-8%, central obesity and reduced HDL-C. MS was evaluated from global changes in parameter values and expressed as a single factorial score following multivariate analysis of each parameter. 213 patients (110 in the pioglitazone group and 103 in the placebo group) were available for intention-to-treat analysis. RESULTS: Pioglitazone-treated patients showed a significant increase in HDL-C compared to placebo group (6.3 mg/dl vs 3.0 mg/dl; p<0.01) in addition to a greater reduction in the extent of MS (-13.2 vs -4.9; p=0.0055). Upon study completion, patients treated with pioglitazone had lower levels of HbA1c (6.41±0.65 vs 6.96±0.74%; p<0.001) and homeostasis model assessment-insulin resistance (HOMA-IR) (2.88±1.95 vs 4.68±3.63; p=0.013) and a reduction of the atherogenic LDL subfraction (pattern B) (-5.7%). CONCLUSIONS: The beneficial effects observed in pioglitazone-treated patients in the present study, (i.e. the increase in HDL-C and the reduction of insulin resistance and atherogenic LDL subfractions), support findings from the PROactive trial, where pioglitazone showed pleiotropic effects and reduced death, fatal myocardial infarction (MI) and non-fatal MI in T2DM patients with MS. Furthermore, medication used in this study showed good tolerability.

Safety and efficacy of insulin aspart and soluble human insulin in Type 2 diabetes mellitus.

AIM: The UpGrade study evaluated the safety profile and effectiveness of insulin aspart (IAsp, NovoRapid®) and soluble human insulin (SHI) in patients with Type 2 diabetes mellitus, under current clinical practice conditions. METHODS: This 26-week, open-label, non-randomized, observational safety study recruited patients using insulin ± metformin and having received ≥ 2 injections of IAsp or SHI over a period of 3 months to 3 years. Data were collected via patient recall and treatment diaries, at baseline, 13- and 26-week visits. The number of major hypoglycemic episodes was the primary endpoint. Secondary endpoints were minor hypoglycemic episodes, HbA1c, fasting and post-prandial blood glucose. RESULTS: Overall, 4099 patients were included. At study end the incidence of major hypoglycemia was low (mean rate 0.117 ev/pt-y) and rates were lower in subjects using IAsp compared with those using SHI, for both major (0.115 vs. 0.121) and minor (6.648 vs. 9.530) episodes. IAsp correlated with a significantly lower risk of minor hypoglycemic episodes (IRR=0.64, P<0.0001). Overall, HbA1c levels decreased across 26 weeks (7.97% to 7.63%, P<0.0001); IAsp had greater HbA1c reduction than SHI (-0.39% and -0.22%, respectively) and was associated with a marginally significant likelihood (vs. SHI) of achieving HbA1c reduction of ≥ 0.5% (OR=1.22, P=0.059). CONCLUSION: Under current clinical practice conditions, treatment of patients with Type 2 diabetes mellitus using either IAsp or SHI resulted in low rates of major hypoglycemia after 26 weeks. Patients using IAsp had a better clinical safety profile and a greater reduction in HbA1c compared with patients using SHI.

[Malnutrition in the elderly: clinical features, psychological and social determinants. Preliminary results]. / La malnutrizione in età geriatrica: caratteristiche cliniche e determinanti psico-sociali (MEG). Risultati preliminari.

In industrialized Countries malnutrition is a very frequent condition in frail groups of the population, people with low income and elderly subjects above all if institutionalized. The aim of the study is to: analyse the prevalence of malnutrition in a sample of elderly people located in different geographical areas in Italy; identify the psychological, social, economic, environmental, cultural and demographic determinants of malnutrition. The prevalence of malnutrition (estimated through the MNA) is high in both sexes (28% of F and 21.9% of M. Age, institutionalisation, health status, autonomy status, cognitive status and education level are some of the factors that correlate with the presence of malnutrition. Loneliness and poverty seem to have a negative impact on nutritional status but further data are needed to confirm this hypothesis. The data collected confirm the need to activate services dedicated to assess the nutritional status of elderly people, to implement campaigns in particular on food education for the elderly population, to set tools and guide lines for caregivers.

Resistin levels and inflammatory and endothelial dysfunction markers in obese postmenopausal women with type 2 diabetes mellitus.

BACKGROUND: Obesity-associated coronary heart disease (CHD) risk is higher in women than in men with type 2 diabetes (T2DM). Resistin, an adipokine secreted by adispose tissue, may contribute to this higher risk. AIMS: To explore the relationships among resistin levels and common inflammatory and endothelial dysfunction markers and CHD risk in obese post-menopausal T2DM women. METHODS: Serum levels of resistin, hsCRP, IL-6, Soluble vascular cell adhesion molecule (sVCAM), homocysteine (tHcy), HOMA-IR and metabolic parameters were determined in a group of 132 T2DM women with and without documented CHD and in 55 non-diabetic women. RESULTS: Resistin, sVCAM, IL-6 and tHcy levels were comparable in T2DM and controls. CHD women showed higher resistin, sVCAM and tHcy levels than those without CHD, and for resistin this difference remained significant after age-adjustment (P = 0.013); conversely hsCRP were ~ 2X higher in T2DM women than in controls (P = 0.0132) without any difference according to CHD history. At univariate analysis resistin levels were significantly associated with age, waist circumference, hypertension, tHcy, hsPCR, sVCAM, IL-6, HDL-cholesterol, triglycerides and creatinine levels, but only creatinine, triglycerides, hsCRP, IL-6 and sVCAM were independently associated to resistin levels at stepwise regression analysis. Resistin levels were independently associated to CHD, increasing the risk by 1.15 times (0.986-1.344 95% CI), together with age, tHcy, LDL-C and hypertension. CONCLUSIONS: Circulating resistin levels were comparable in obese/overweight T2DM and control women. In T2DM women, resistin levels correlated with markers of renal function, systemic inflammation and endothelial dysfunction and were independently associated with a higher CHD risk.

Similar glycaemic control and risk of hypoglycaemia with patient- versus physician-managed titration of insulin glargine 300 U/mL across subgroups of patients with T2DM: a post hoc analysis of ITAS.

AIMS: The Italian Titration Approach Study (ITAS) demonstrated comparable HbA1c reductions and similarly low hypoglycaemia risk at 6 months in poorly controlled, insulin-naïve adults with T2DM who initiated self- or physician-titrated insulin glargine 300 U/mL (Gla-300) in the absence of sulphonylurea/glinide. The association of patient characteristics with glycaemic and hypoglycaemic outcomes was assessed. METHODS: This post hoc analysis investigated whether baseline patient characteristics and previous antihyperglycaemic drugs were associated with HbA1c change and hypoglycaemia risk in patient- versus physician-managed Gla-300 titration. RESULTS: HbA1c change, incidence of hypoglycaemia (any type) and nocturnal rates were comparable between patient- and physician-managed arms in all subgroups. Hypoglycaemia rates across subgroups (0.03 to 3.52 events per patient-year) were generally as low as observed in the full ITAS population. Small increases in rates of 00:00-pre-breakfast and anytime hypoglycaemia were observed in the ≤ 10-year diabetes duration subgroup in the patient- versus physician-managed arm (heterogeneity of effect; p < 0.05). CONCLUSIONS: Comparably fair glycaemic control and similarly low hypoglycaemia risk were achieved in almost all patient subgroups with patient- versus physician-led Gla-300 titration. These results reinforce efficacy and safety of Gla-300 self-titration across a range of phenotypes of insulin-naïve people with T2DM. CLINICAL TRIAL REGISTRATION: EudraCT 2015-001167-39.

Very high frequency of the polymorphism for the insulin receptor substrate 1 (IRS-1) at codon 972 (glycine972arginine) in Southern Italian women with polycystic ovary syndrome.

A major component of the polycystic ovary syndrome (PCOS) is the insulin resistance. Only a few studies have evaluated the IRS-1 polymorphism at codon 972, sometimes in the absence of a control group, and with great variability in frequency (0-23% in PCOS vs. 0-17% in controls), and with no unequivocal relationships between the polymorphism and clinical or biochemical indexes. The aim of the work was to evaluate the frequency of the IRS-1 polymorphism at codon 972 in PCOS, and correlate it to clinical and biochemical indexes. We assessed the rs 1801278 polymorphic variant in the IRS-1 gene (Gly972Gly=wild-type; Gly972Arg=heterozygosity; Arg972Arg=homozygosity) in genomic DNA by restriction fragment length polymorphism. The study was conducted at an academic medical center with the participation of 65 women with PCOS and 27 age-matched healthy women (controls). Compared to controls, Gly972Arg was very frequent in PCOS (77% vs. 18%, p<0.0001); one PCOS woman was homozygous. Compared to wild-type PCOS, heterozygous PCOS women had only three significantly different indexes: higher fasting insulin, insulin resistance index, and lower 120 min OGTT glucose. Moreover, in the correlation analysis between any two clinical or biochemical variables, the Pearson's correlation coefficients were frequently of different magnitude in heterozygous PCOS versus wild-type PCOS. Overall, heterozygous PCOS had a greater number of statistically significant relationships between different clinical, metabolic and hormonal indexes: 44 direct and 9 inverse versus 6 and 3, respectively. The IRS-1 Gly972Arg has the highest frequency reported world-wide for PCOS women. This variant is associated with insulin resistance and higher fasting insulin in PCOS women.

Obesity and changes in urine albumin/creatinine ratio in patients with type 2 diabetes: the DEMAND study.

BACKGROUND AND AIMS: Obesity is a potential risk factor for renal disease in non-diabetic subjects. It remains unclear whether this also applies to diabetic patients. We investigated whether obesity predicted changes in albumin excretion rate in individuals with type 2 diabetes. METHODS AND RESULTS: Fifty Italian diabetes outpatient clinics enrolled a random sample of 1289 patients. A morning spot urine sample was collected to determine urinary albumin/creatinine ratio (ACR) at baseline and after 1 year from the study initiation. Progression of albumin excretion was defined as a doubling in ACR, while regression was defined as a 50% reduction. Multivariate logistic regression analyses were used to evaluate correlates of these outcomes. Data are expressed as odds ratios (OR) with 95% confidence intervals (CI). The risk of progression increased by 7% (OR=1.07; 95%CI 1.00-1.15) for every 5-cm increase in waist circumference measured at baseline, and by 17% (OR=1.17; 95%CI 1.03-1.33) for every one-unit increase in BMI during follow-up. The likelihood of regression was not independently associated with any of the variables investigated. The effect of obesity on progression of ACR was independent of metabolic control, blood pressure, treatment, and baseline level of albumin excretion. CONCLUSIONS: We found a tight link between obesity and changes in albumin excretion in diabetic subjects, suggesting potential benefits of interventions on body weight on end-organ renal damage.

Three different premixed combinations of biphasic insulin aspart - comparison of the efficacy and safety in a randomized controlled clinical trial in subjects with type 2 diabetes.

AIM: To evaluate clinical efficacy and safety of biphasic insulin aspart (BIAsp) 30 twice daily (b.i.d.) vs. BIAsp 50 or BIAsp 70 (high-mix regimens) thrice daily (t.i.d.) all in combination with metformin in a 36-week clinical trial in subjects with type 2 diabetes. METHODS: Efficacy measurements included haemoglobin A(1c) (HbA(1c)) and eight-point plasma glucose (PG); safety included adverse events (AEs) and hypoglycaemic episodes. The three treatment groups (approximately 200 subjects in each group) were well matched regarding sex ratio, ethnicity, age and body mass index. RESULTS: After 12 weeks, 43% and 54% in the BIAsp 50 and 70 groups, respectively, switched their dinner insulin to BIAsp 30. Both high-mix regimens were non-inferior to BIAsp 30 b.i.d., as measured by change in HbA(1c), and the BIAsp %50 regimen was superior. The odds for meeting the American Diabetes Association and The American Association of Clinícal Endocrinologist HbA(1c) targets of <7% and < or =6.5%, respectively, were significantly higher with the BIAsp 50 regimen than with BIAsp 30. A significantly lower PG level was achieved from lunch until 02:00 hours with both high-mix regimens compared with BIAsp 30 b.i.d. AEs were mild or moderate with all three regimens. Frequency of hypoglycaemic episodes was comparable for the BIAsp 50 and the BIAsp 30 b.i.d. regimens but was significantly higher with BIAsp 70 t.i.d. CONCLUSIONS: Glycaemic control improved with BIAsp 50 t.i.d. without higher incidence of hypoglycaemia compared with BIAsp 30 b.i.d.; with BIAsp 70 t.i.d. lower PG levels from lunch to 02.00 hours, but more hypoglycaemic episodes were obtained compared with BIAsp 30 b.i.d.